The human skin microbiota is complex and dynamic. It plays a significant role in defending against pathogens by interacting with the host immune system. To understand the dynamics of the skin microbial community and the effect on the human health upon its perturbation, we propose to study the population dynamics of a major skin commensal, Propionibacterium acnes, and its phages in pilosebaceous units (hair follicles). One of the diseases associated with pilosebaceous units is acne. Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting P. acnes has been a mainstay treatment for more than 30 years. Our preliminary study shows that microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome and its dynamics at the subspecies/population level. Previously, by 16S rDNA analysis, we found that certain P. acnes ribotypes are highly enriched in acne, and in contrast, certain ribotype is over-represented in healthy skin. This indicates that studying the structure and dynamics of the microbial community offers promise for understanding the correlation between the microbial community and human health and disease. In this project, we plan to investigate in three directions the dynamics of th microbiome in pilosebaceous units. First, we plan to define the population structure and dynamics of P. acnes in microcomedones and examine whether they are different in health and acne. Second, we plan to determine whether predator-prey population dynamics exist between P. acnes and P. acnes phages and whether the dynamics are different in health and acne. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host and determine whether changes in the microbial community alter the host immune responses. This proposed study will define the population structure and dynamics of P. acnes and its phages in the pilosebaceous units of healthy individuals and acne patients and their interactions with the host. The findings from the study will address a fundamental gap in our knowledge of the skin microbiome and may lead to further studies for the development of innovative clinical approaches to treating, preventing and managing the disease. PUBLIC HEALTH RELEVANCE: Human skin provides the first line of defense against pathogens. The goal of this project is to investigate the dynamics of the microbial community residing underneath the surface of human skin and its association with acne, a common skin disease affecting 17 million Americans; more than 80% of the people of age 12-24. Success in this project may lead to the development of new effective therapeutic strategies for treatment of acne.